{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T03:18:18Z","timestamp":1768879098436,"version":"3.49.0"},"reference-count":31,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Adenocarcinomas of the esophagogastric and gastric areas are often managed with a multimodal treatment including neoadjuvant chemotherapy and surgery. The impact of neoadjuvant chemotherapy on the host\u2019s antitumoral immune response remains largely unknown. Methods: A retrospective review of a single-institution cohort of patients with adenocarcinoma of the stomach or esophagogastric area undergoing curative intent surgery after neoadjuvant chemotherapy FLOT (Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel) was reviewed. After institutional ethics approval, pathologic slides were re-reviewed and tumor-infiltrating lymphocyte scores were calculated. Tumor-infiltrating lymphocytes (TILs) were studied in conjunction with tumor regression scores (TRG) and the degree of regression in the involved lymph nodes as well as in correlation with the lymph node ratio (the ratio of involved lymph nodes over the total number of lymph nodes resected). Results: A total of 106 patients were reviewed. No statistical correlation could be established between the tumor-infiltrating lymphocyte scores and the degree of regression in the primary tumor as well as with the partial response to chemotherapy of pathologically involved lymph nodes. The TIL score also did not correlate with the lymph node ratio in our patient cohort. A strong correlation was noted between TILs and lymph nodes that completely regressed after neoadjuvant chemotherapy. Conclusions: Tumor-infiltrating lymphocytes do not correlate with the response of the primary tumor or the partial response of the involved lymph nodes, but only with the complete response to neoadjuvant chemotherapy of tumor-involved lymph nodes. Our study focuses on the effects of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes compared to the effects on the primary tumor and the involved lymph nodes.<\/jats:p>","DOI":"10.3390\/cancers17121971","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T03:53:12Z","timestamp":1749786792000},"page":"1971","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tumor-Infiltrating Lymphocytes Demonstrate Distinct Behavior in the Tumoral and Peritumoral Microenvironment After Neoadjuvant Chemotherapy in Patients with Resected Adenocarcinoma of the Gastric or Gastroesophageal Junction: Results from a Single Center"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1196-5388","authenticated-orcid":false,"given":"Fotios","family":"Seretis","sequence":"first","affiliation":[{"name":"First Propaedeutic Department of Surgery, Hippokrateion General Hospital of Athens, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Panagaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, \u201cKonstantopouleio-Patision\u201d General Hospital of Nea Ionia, 14233 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Ritsatou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hippokrateion General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni","family":"Stoupi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hippokrateion General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Theodorou","sequence":"additional","affiliation":[{"name":"First Propaedeutic Department of Surgery, Hippokrateion General Hospital of Athens, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5582-0530","authenticated-orcid":false,"given":"Spyridon","family":"Smparounis","sequence":"additional","affiliation":[{"name":"First Propaedeutic Department of Surgery, Hippokrateion General Hospital of Athens, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1198-4901","authenticated-orcid":false,"given":"Chrysoula","family":"Glava","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hippokrateion General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Theochari","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hippokrateion General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Triantafyllou","sequence":"additional","affiliation":[{"name":"First Propaedeutic Department of Surgery, Hippokrateion General Hospital of Athens, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1038\/s41416-023-02257-3","article-title":"Tumour infiltrating lymphocytes and survival after adjuvant chemotherapy in patients with gastric cancer: Post-hoc analysis of the CLASSIC trial","volume":"128","author":"Liu","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.gassur.2023.12.002","article-title":"Prognostic implications of tumor-infiltrating lymphocytes within the tumor microenvironment in gastric cancer","volume":"28","author":"Pereira","year":"2024","journal-title":"J. Gastrointest. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102510","DOI":"10.1016\/j.clinre.2024.102510","article-title":"Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: A systematic review and meta-analysis","volume":"49","author":"Cao","year":"2024","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.pathol.2016.10.005","article-title":"High intratumoural but not peritumoural inflammatory host response is associated with better prognosis in primary resected oesophageal adenocarcinomas","volume":"49","author":"Stein","year":"2017","journal-title":"Pathology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1007\/s12094-021-02556-2","article-title":"Distribution of tumor-infiltrating-T-lymphocytes and possible tumor-escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus","volume":"23","author":"Schoemmel","year":"2021","journal-title":"Clin. Transl. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s13304-023-01497-5","article-title":"Facing adenocarcinoma of distal esophagus and esophagogastric junction: A CROSS versus FLOT propensity score-matched analysis of oncological outcomes in a high-volume institution","volume":"75","author":"Lombardi","year":"2023","journal-title":"Updates Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4522","DOI":"10.1200\/JCO.23.00139","article-title":"Pathologic Lymph Node Regression After Neoadjuvant Chemotherapy Predicts Recurrence and Survival in Esophageal Adenocarcinoma: A Multicenter Study in the United Kingdom","volume":"41","author":"Moore","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1954807","DOI":"10.1080\/2162402X.2021.1954807","article-title":"Pre-treatment tumor-infiltrating T cells influence response to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma","volume":"10","author":"Goedegebuure","year":"2021","journal-title":"Oncoimmunology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yu, W., Wang, S., Rong, Q., Ajayi, O.E., Hu, K., and Wu, Q. (2022). Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis. Genes, 13.","DOI":"10.3390\/genes13061017"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mak, T.K., Li, X., Huang, H., Wu, K., Huang, Z., He, Y., and Zhang, C. (2022). The cancer-associated fibroblast-related signature predicts prognosis and indicates immune microenvironment infiltration in gastric cancer. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.951214"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1159\/000531475","article-title":"Infiltration of Gastric Cancer Stroma by Tumor-Infiltrating Lymphocytes Correlates with Mechanistic Target of Rapamycin Signaling","volume":"101","author":"Nakazawa","year":"2023","journal-title":"Oncology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/annonc\/mdu450","article-title":"The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: Recommendations by an International TILs Working Group 2014","volume":"26","author":"Salgado","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"znae034","DOI":"10.1093\/bjs\/znae034","article-title":"Prognostic value of Mandard score and nodal status for recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma","volume":"111","author":"Henckens","year":"2024","journal-title":"Br. J. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Seretis, F., Glava, C., Smparounis, S., Riga, D., Karantzikos, G., Theochari, M., Theodorou, D., and Triantafyllou, T. (2024). Tumor-Infiltrating Lymphocytes in Resected Esophageal and Gastric Adenocarcinomas Do Not Correlate with Tumor Regression Score After Neoadjuvant Chemotherapy: Results of a Case-Series Study. Cancers, 16.","DOI":"10.3390\/cancers16213694"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Jannasch, O., Schwanz, M., Otto, R., Mik, M., Lippert, H., and Mroczkowski, P. (2025). Lymph Node Yield and Lymph Node Ratio for Prognosis of Long-Term Survival in Gastric Carcinoma. Cancers, 17.","DOI":"10.3390\/cancers17030414"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12957-022-02507-3","article-title":"Association of tumor deposits with tumor-infiltrating lymphocytes and prognosis in gastric cancer","volume":"20","author":"Li","year":"2022","journal-title":"World J. Surg. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.1002\/cam4.2963","article-title":"Tumor deposit serves as a prognostic marker in gastric cancer: A propensity score-matched analysis comparing survival outcomes","volume":"9","author":"Wenquan","year":"2020","journal-title":"Cancer Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e11387","DOI":"10.1097\/MD.0000000000011387","article-title":"Association between density of tumor-infiltrating lymphocytes and prognoses of patients with gastric cancer","volume":"97","author":"Yu","year":"2018","journal-title":"Medicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1111\/his.13781","article-title":"Tumour deposits are a significant prognostic factor in gastric cancer\u2014A systematic review and meta-analysis","volume":"74","author":"Knijn","year":"2019","journal-title":"Histopathology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1245\/s10434-012-2692-9","article-title":"Perigastric tumor deposits in primary gastric cancer: Implications for patient prognosis and staging","volume":"20","author":"Lee","year":"2013","journal-title":"Ann. Surg. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/bjs.5240","article-title":"Extranodal metastasis is an indicator of poor prognosis in patients with gastric carcinoma","volume":"93","author":"Etoh","year":"2006","journal-title":"Br. J. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Huang, X., Feng, D., Mitra, S., Andretta, E.S., Hooshdaran, N.B., Ghelani, A.P., Wang, E.Y., Frost, J.N., Lawless, V., and Vancheswaran, A. (2025). Opposing Functions of Distinct Regulatory T Cell Subsets in Colorectal Cancer. bioRxiv.","DOI":"10.1101\/2025.02.07.637083"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.ejso.2021.08.016","article-title":"Expression of programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand (PD-L1) in adenocarcinomas of the gastroesophageal junction change significantly after neoadjuvant treatment","volume":"48","author":"Jomrich","year":"2022","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1111\/cas.12938","article-title":"Negative influence of programmed death-1-ligands on the survival of esophageal cancer patients treated with chemotherapy","volume":"107","author":"Tanaka","year":"2016","journal-title":"Cancer Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.annonc.2024.11.016","article-title":"Tremelimumab and durvalumab as neoadjuvant or non-operative management strategy of patients with microsatellite instability-high resectable gastric or gastroesophageal junction adenocarcinoma: The INFINITY study by GONO","volume":"36","author":"Raimondi","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102177","DOI":"10.1016\/j.ctrv.2021.102177","article-title":"Total neoadjuvant therapy for rectal cancer: Making sense of the results from the RAPIDO and PRODIGE 23 trials","volume":"96","author":"Giunta","year":"2021","journal-title":"Cancer Treat. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8616","DOI":"10.1245\/s10434-024-16030-0","article-title":"Clinical and Pathologic Response to Neoadjuvant Immunotherapy in DNA Mismatch Repair Protein-Deficient Gastroesophageal Cancers","volume":"31","author":"Shannon","year":"2024","journal-title":"Ann. Surg. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100531","DOI":"10.1016\/j.medj.2024.10.008","article-title":"Neoadjuvant cadonilimab plus FLOT chemotherapy in locally advanced gastric\/gastroesophageal junction adenocarcinoma: A multicenter, phase 2 study","volume":"6","author":"Long","year":"2025","journal-title":"Med"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1158\/0008-5472.CAN-24-2697","article-title":"Combining Apatinib and Oxaliplatin Remodels the Immunosuppressive Tumor Microenvironment and Sensitizes Desert-Type Gastric Cancer to Immunotherapy","volume":"85","author":"Lin","year":"2025","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Li, Y., Cao, Y., Wang, X., Li, C., Zhao, L., and Li, H. (2025). Effects of perioperative treatment of resectable adenocarcinoma of esophagogastric junction by immunotherapy (Adebrelimab) combined with chemotherapy (XELOX): Protocol for a single-center, open-labeled study (AEGIS trial, neoadjuvant immunochemotherapy). BMC Cancer, 25.","DOI":"10.1186\/s12885-025-13589-z"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.annonc.2024.10.829","article-title":"Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and\/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study","volume":"36","author":"Lordick","year":"2025","journal-title":"Ann. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/12\/1971\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:51:10Z","timestamp":1760032270000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/12\/1971"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,13]]},"references-count":31,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["cancers17121971"],"URL":"https:\/\/doi.org\/10.3390\/cancers17121971","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,13]]}}}